14073-07-5Relevant academic research and scientific papers
Synthesis and bioevaluation of a series of α-pyrone derivatives as potent activators of Nrf2/ARE pathway (part I)
Xi, Mei-Yang,Sun, Zhong-Ying,Sun, Hao-Peng,Jia, Jian-Min,Jiang, Zheng-Yu,Tao, Lei,Ye, Ming,Yang, Xi,Wang, Ya-Jing,Xue, Xin,Huang, Jing-Jie,Gao, Yuan,Guo, Xiao-Ke,Zhang, Sheng-Lie,Yang, Ying-Rui,Guo, Qing-Long,Hu, Rong,You, Qi-Dong
, p. 364 - 371 (2013)
When exposed to electrophiles, human colorectal cancer cells (HCT116) counteract oxidative stress through activating NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway. To identify new activators, luciferase reporter gene assay was used to screen in-house database of our laboratory, leading to a novel α-pyrone compound 1 as a hit. 2 with 2-fluoro phenyl group exhibited the strongest ARE inductive activity in the first round structure-activity relationship (SAR) study. Biological studies showed the compound induced nuclear translocation of Nrf2 preceded by phosphorylation of ERK1/2. The data encouraged us to use 2 as lead and 20 derivatives were synthesized to discuss a more detailed SAR, leading to a more potent compound 9, which can be the starting compound for further modification.
